Loss of Functional Suppression by CD4+CD25+ Regulatory T Cells in Patients with Multiple Sclerosis

By V. Viglietta, C. Baecher-Allan, Howard L. Weiner, David A. Hafler. Journal of Experimental Medicine, 2004

1,943 citations recorded by the source corpus.

CD4+CD25+ regulatory T cells contribute to the maintenance of peripheral tolerance by active suppression because their deletion causes spontaneous autoimmune diseases in mice. Human CD4+ regulatory T cells expressing high levels of CD25 are suppressive in vitro and mimic the activity of murine CD4+CD25+ regulatory T cells. Multiple sclerosis (MS) is an inflammatory disease thought to be mediated by T cells recognizing myelin protein peptides. We hypothesized that altered functions of CD4+CD25hi regulatory T cells play a role in the breakdown of immunologic self-tolerance in patients with MS. Here, we report a significant decrease in the effector function of CD4+CD25hi regulatory T cells from peripheral blood of patients with MS as compared with healthy donors. Differences were also apparent in single cell cloning experiments in which the cloning frequency of CD4+CD25hi T cells was significantly reduced in patients as compared with normal controls. These data are the first to demonstrate alterations of CD4+CD25hi regulatory T cell function in patients with MS.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/231c890d95d9b24425874b5a94d32f764df3b1ee

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In Immunology

1. Shimon Sakaguchi
2. V. Kuchroo
3. K. Wing
4. M. Oukka
5. T. Korn
6. M. Battaglia
7. M. Miyara
8. Tomoyuki Yamaguchi

Citations in the corpus

• IL-12 p40 monomer is different from other IL-12 family members to selectively inhibit IL-12Rβ1 internalization and suppress EAE (2020, background): “It has been reported that Tregs become both numerically and functionally imperfect during autoimmune insults (25, 26).”
• Natural Recovery and Protection from Autoimmune Encephalomyelitis: Contribution of CD4+CD25+ Regulatory Cells within the Central Nervous System1 (2005, background): “It has recently been reported that CD4 CD25 cells from multiple sclerosis patients have an intrinsically reduced regulatory activity (35).”
• The PD-1 Pathway in Tolerance and Autoimmunity (2010, background): “(91) first reported a functional defect in CD4CD25 T cells isolated from peripheral blood of MS patients.”
• Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. (2009, background): “They play crucial roles in human diseases, such as autoimmune disease, allergy, and cancer (Curiel et al., 2004; Ehrenstein et al., 2004; Kriegel et al., 2004; Miyara et al., 2005; Viglietta et al., 2004).”
• Evolutionary Causes and Consequences of Immunopathology (2005, background): “T regulatory cells also protect against other forms of immunopathology, including Type 1 autoimmune attack of the central nervous system in multiple sclerosis (Viglietta et al. 2004) and Type 2 A nn u.”
• Compromised Function of Regulatory T Cells in Rheumatoid Arthritis and Reversal by Anti-TNFα Therapy (2004, background): “Indeed, it has been reported recently that regulatory T cells isolated from the PB of patients with multiple sclerosis are functionally defective in terms of their ability to suppress proliferation and cytokines production by activated T cells (23).”
• The X-files in immunity: sex-based differences predispose immune responses (2008, background): “In addition, T Reg -cell functional deficits have been implicated in autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis 22, 23 .”
• Dysfunctional Blood and Target Tissue CD4+CD25high Regulatory T Cells in Psoriasis: Mechanism Underlying Unrestrained Pathogenic Effector T Cell Proliferation1 (2005, background): “3B), similar to what was recently reported for both multiple sclerosis and autoimmune polyglandular syndrome type II (38, 39).”
• Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. (2008, background): “In MS, regulatory CD4 CD25 T cells are present in normal numbers in the peripheral blood, but they show impaired function in comparison with control individuals.(49) Therefore, if functionally impaired regulatory T cells are relevant to MS pathogenesis they must be exerting their influence outside t”
• CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients. (2010, background): “Defects in regulatory T cells have been identified in several autoimmune diseases including rheumatoid arthritis (RA), multiple sclerosis (MS), and SLE (Ehrenstein et al., 2004; Viglietta et al., 2004).”